The purpose of this study was to determine the predictors of bone mineral density (BMD), bone mineral content (BMC), and bone turnover markers in obese postmenopausal women. In this cross-sectional study, 81 postmenopausal women aged 58.40 ± 6.08 years were analyzed. Anthropometric parameters were recorded. Serum glucose parameters, serum lipid profiles, adipokines, renal, hepatic parameters, and bone markers concentrations were determined by well-validated laboratory routine methods. BMD, BMC, and body composition were measured by Dual X-ray Absorptiometry. We found a significant correlation of BMD with age, years since menopause, anthropometric parameters, glycemia, alkaline phosphatase, fat mass, and lean mass. Multiple regression analysis demonstrated that years since menopause, waist circumference, alkaline phosphatase, trunk fat, and lean mass were independently associated to BMD. Also, age, years since menopause, anthropometric parameters, total cholesterol, alkaline phosphatase, fat mass, and lean mass were correlated to BMC. However, only waist circumference and trunk fat were independently related to BMC. Bone turnover markers were significantly correlated to the age, glycemia, HbA1c, adipokines, hepatic parameters, and lean mass. Nevertheless, only adipokines, gamma glutamyl transferase (GGT), and alkaline phosphatase were independently associated to bone turnover markers. These observations suggest that number of years since menopause, waist circumference, alkaline phosphatase, trunk fat, and lean mass were the only significant predictors of BMD. However, waist circumference seems to be a stronger predictor than trunk fat for BMC. Moreover, adiponectin, resistin, GGT, and alkaline phosphatase were significant predictors of the bone resorption (CTX-I) and the bone formation (P1NP) markers.

To analyze the interdependent relationship between serum bone metabolic markers and traditional Chinese medicine (TCM) syndromes in patients with chronic kidney disease (stages 3 and 4)-related mineral and bone disorder (CKD-MBD), in order to provide the objective basis for exploring the rules of TCM syndrome differentiation in patients with CKD-MBD. The retrospective survey was conducted to collect 105 cases with CKD (stages 3 and 4)-MBD. General clinical indexes, frequency of TCM syndromes and distribution of TCM syndrome type were investigated. Furthermore, serum bone metabolic markers, including calcium (Ca2+), phosphonium (P3+), intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), procollagen type 1 amino-N-terminal propeptide (P1NP) and β-crosslaps (β-CTX) were analyzed, respectively. Meanwhile, bone mineral density (BMD) was assessed. And then, the multivariate regression analysis was performed for serum bone metabolic markers and TCM syndromes. The results showed that the general clinical features of the 105 patients included old age, hypertension, fracture, loss of bone mass and mild abnormalities of serum bone metabolic markers. High-frequency TCM syndromes were related to Yang deficiency in Spleen and Kidney, Qi deficiency in Spleen and Kidney and blood stasis. Moreover, Yang deficiency in Spleen and Kidney and blood stasis were found as the most frequent characteristics of the distribution of TCM syndromes type. The clinical characteristics of patients with the syndrome type of Yang deficiency in Spleen and Kidney were probably old age, increase in TCM syndrome scores and abnormalities in iPTH and P1NP. In addition, the interdependent relationship between abnormality in Ca2+ and syndromes of hair loss, tooth shake and sexual dysfunction, abnormality in P3+ and syndromes of aches in waist and knees, abnormality in iPTH and syndromes of soreness and weakness in waist and knees, lassitude, fatigue and extreme chilliness, abnormality in ALP and syndromes of loose stools, abnormality in P1NP and syndromes of fear of chills, tendency of warmth and loose stools, and abnormality in β-CTX and syndromes of chills and pain in waist and knees. In general, among the 105 cases with CKD (stages 3 and 4)-MBD were clinically characterized by mild changes in serum bone metabolic markers; And their main TCM syndrome was the deficiency in spleen and kidney. Serum bone metabolic markers with mild changes have an interdependent relationship with main TCM syndromes, and can be considered as an objective syndrome factor of TCM syndrome differentiation.

Objective With the aging of society, both osteoporosis and fatty liver disease (FLD) are becoming important issues. However, the relationship between osteoporosis and FLD remains controversial. We investigated the association between bone metabolism and FLD in a Japanese community in a cross-sectional study. Methods A total of 1,020 participants were enrolled in a health survey. FLD was diagnosed by ultrasonography. Bone metabolism was evaluated based on bone mineral density (BMD), which was assessed using dual-energy X-ray absorptiometry, and with the bone formation index (total type I procollagen N-terminal propeptide/bone-alkaline phosphatase ratio; P1NP/BAP ratio) and the bone resorption index (crosslinked N-telopeptide of type I collagen/tartrate-resistant acid phosphatase-5b ratio; NTx/TRACP-5b ratio) calculated from serum bone turnover markers. Results The BMD (percentage of the young adult mean) was the same level in both male and female participants with and without FLD. Both men and women showed an age-dependent decrease in their bone formation index and bone resorption index values. Men of ≥70 years of age and women of 60-69 years of age with FLD had significantly lower bone formation index values and higher bone resorption index values. However, similar findings were not seen in women of ≥70 years of age. Conclusion Although the BMD levels were the same, regardless of the presence or absence of FLD, elderly participants with FLD showed decreased bone formation and increased bone resorption, with sex differences. Because our results suggest that FLD in elderly individuals is detrimental for bone metabolism, and that it leads to bone loss and osteoporosis, further studies using a cohort population are warranted.

Background Bone turnover markers (BTMs) may provide insight into bone health in young women, but have been little studied in this demographic. We aimed to explore the association between body composition, hormonal contraception, bone mineral density and biochemical parameters and BTMs in young women. Methods Participants were community-dwelling females aged 16-25 years, living in Victoria, Australia. Carboxy-terminal cross-linking telopeptide of type 1 collagen (CTX) and total procollagen type 1 N-propeptide (P1NP) were analysed on the Roche Elecsys automated analyzer. A total of 305 were evaluated, after excluding participants with medical conditions or medications (except hormonal contraceptives), which may affect bone metabolism. Results Median (Q1, Q3) BTM values were 540 (410, 690) ng/L for CTX and 61.7 (46.2, 83.7) µg/L for P1NP. Serum CTX and P1NP were inversely associated with chronological age ( P < 0.001), transferrin ( P < 0.020) and serum dehydroepiandrosterone sulphate concentration ( P < 0.001). BTM values were up to 22% lower in combined oral contraceptive (COC) pill users ( P < 0.001). Serum CTX was inversely associated with per cent body fat ( P = 0.009) and tibial cortical volumetric bone mineral density (vBMD; P = 0.003). Serum P1NP concentrations were 23 µg/L higher in participants who reported using an osteopath in the previous year ( P = 0.007). Conclusions These data suggest that BTMs are influenced by age, COC use, body composition, iron status and hormonal profiles. Higher CTX values were associated with lower tibial cortical vBMD. Examining BTMs in relation to interventions aimed at improving bone health in young women is warranted.

To evaluate the efficacy of combined medication of risedronate sodium and raloxifene, a selective estrogen receptor modulator (SERM) on the postmenopausal osteoporosis (PMOP). PMOP patients underwent the combined medication of risedronate sodium and raloxifene (SERM, Treatment group), or only medication of risedronate sodium (Control group). After medication, more significant increases were observed in the bone densities of the lumber vertebra (L<inf>1-4</inf>) and the neck of left femur of patients in the treatment group. Simultaneously, the levels of estrogen and progesterone in serum decreased sharply in the treatment group. After treatment, P1NP and β-CTX levels in serum decreased significantly in two groups in comparison with the levels prior to treatment, with evident elevations in the levels of BAP and BGP; similarly, ameliorations in the treatment group were much more evident than those in the control group. In addition, significant declines were identified in the VAS scores of two groups after treatment when comparing to the scores prior to the treatment, and the decline in the treatment group was more evident than that in the control group. Combined medication of risedronate sodium and SERM (raloxifene) performs better in treatment of osteoporosis than the single use of risedronate sodium, without the deterioration of adverse effect of medication.

INTRODUCTION There is growing evidence that obstructive sleep apnea (OSA) influences both bone metabolism and structure. Chitinase‑3‑like protein 1 (YKL‑40) is a novel inflammatory and remodeling marker, the levels of which were shown to increase in OSA. YKL‑40 can probably alter the bone turnover. OBJECTIVES The aim of the study was to assess a possible interplay between YKL‑40 and bone turnover markers in patients with different stages of OSA, and to evaluate the relation between bone mass, severity of OSA, and YKL‑40 levels. PATIENTS AND METHODS The study involved 72 male patients with OSA. They were divided into 3 groups according to disease severity, using the apnea-hypopnea index (AHI): group 1 (n = 18; 5≤ AHI <15), group 2 (n = 25; 15≤ AHI <30), and group 3 (n = 29; AHI ≥30). All patients underwent polysomnography and densitometry. Fasting blood samples were collected for YKL‑40, C‑terminal telopeptide of typeI collagen (CTX), procollagen type 1 N‑terminal propeptide (P1NP), and other markers. RESULTS P1NP differed between groups 1 and 2, as well as groups 1 and 3 (P = 0.02). Group 2 had higher CTX levels than group 1 (borderline significance, P = 0.05). A simple linear regression analysis showed that serum YKL‑40 levels were associated with the levels of CTX (P <0.0001, β = 0.9871) and P1NP (P <0.0001, β = 0.9780). CONCLUSIONS Our study might suggest that YKL‑40 is associated with bone turnover in OSA. We may assume that this marker influences both bone formation and destruction; thus, OSA could be characterized by preserved bone mineral density.

OBJECTIVE

To investigate the relationship between bone metabolic indicators and non-alcoholic fatty liver disease (NAFLD) in healthy middle-aged men.

METHODS

The bone metabolic indicators of 232 healthy middle-age men with NAFLD (NAFLD group) and 308 healthy controls without fatty liver (Control group) were measured, including non-collagenous osteocalcin, the procollagen type 1 N-terminal propeptide (P1NP), beta-C-terminal telopeptide of type I collagen (β-CTX). The Student's t-test was used to analyze the differences in the bone metabolic indicators, age, clinical data, biochemical indicators, and the indicators of glucose and lipid metabolism between the two groups. The correlation of fatty liver-related indicators was detected using the logistic regression analysis.

RESULTS

The body mass index (BMI), diastolic blood pressure, and heart rate in NAFLD group were significantly higher than those in Control group. Among the indicators of glucose and lipid metabolism in NAFLD group, the levels of blood glucose [fasting plasma glucose, postprandial blood glucose and hemoglobin A1c (HbA1c)] were significantly higher than those in Control group. In addition, the insulin resistance and secretion indexes were also significantly higher than those in Control group. The levels of lipid metabolic indicators such as triglyceride were higher, but high-density lipoprotein cholesterol was lower than that in Control group. From logistic regression analysis, the BMI, Homeostasis model assessment (HOMA)-β, HOMA-IR, HbA1c and P1NP were positively associated with the occurrence of NAFLD.

CONCLUSIONS

The bone metabolic indicator P1NP might be a potential predicator for the diagnosis of NAFLD in clinical application.

Alkaline phosphatase (ALP) in humans comprises a family of four cell-surface phosphomonoester phosphohydrolase isozymes. Three genes separately encode the "tissue-specific" ALPs whereas the fourth gene encodes ubiquitous homodimeric "tissue-nonspecific" ALP (TNSALP) richly expressed in bone, liver, kidney, and developing teeth. TNSALP monomers have five putative N-linked glycosylation sites where different post-translational modifications account for this isozyme's distinctive physicochemical properties in different organs. Three bone-derived TNSALP (BALP) isoforms (B/I, B1, and B2) are present in healthy serum, whereas a fourth BALP isoform (B1x) can circulate in chronic kidney disease. Herein, we report a healthy boy with persistent hyperphosphatasemia due to BALP levels two- to threefold higher than age-appropriate reference values. High-performance liquid chromatography, electrophoresis, heat inactivation, catalysis inhibition, and polyethylene glycol precipitation revealed increased serum B/I, B1, and B2 differing from patterns found in skeletal diseases. B/I was ~23-fold elevated. Absence of mental retardation and physical stigmata excluded Mabry syndrome, the ALP-anchoring disorder causing hyperphosphatasemia. Routine biochemical studies indicated intact mineral homeostasis. Serum N-terminal propeptide of type I procollagen (P1NP) level was normal, but C-terminal cross-linking telopeptide of type I collagen (CTX) level was elevated. However, radiological studies showed no evidence for a generalized skeletal disturbance. Circulating pyridoxal 5'-phosphate, a TNSALP natural substrate, was not low despite the laboratory hyperphosphatasemia, thereby suggesting BALP phosphohydrolase activity was not elevated endogenously. Mutation analysis of the ALPL gene encoding TNSALP revealed no defect. His non-consanguineous healthy parents had serum total ALP activity and BALP protein levels that were normal. Our patient's sporadic idiopathic hyperphosphatasemia could reflect altered post-translational modification together with increased expression and/or impaired degradation of BALP.

Keywords: ALPL gene; Bone; Enzymopathy; Hypophosphatasia; Isoenzyme; Isoform; Isozyme; Mabry syndrome; Osteoblast; Phosphohydrolase; Pyridoxal 5′-phosphate; Skeleton; Vitamin B(6).

Objective: To investigate the relevance ratio of osteoporosis and bone mass of middle aged and elderly people in Beijing communities, in order to understand occurrence and development trend of abnormality of bone mass in high-risk population from community.

Methods: Based on the method of cross-sectional investigation, the information data of 1 540 middle-aged and elderly people from 10 communities were collected, including 415 males and 1 125 females, aged from 45 to 80 years old with the average of (63.02±7.15) years old; the height was (161.34±7.24) cm, the weight was (65.90±10.19) kg, body mass index was (25.29±3.32) kg /m2. Bone mineral density (BMD) of lumbar vertebrae (L₁-L₄) and both hips were measured by dual energy X ray absorptiometry (DEXA). The differences of bone mineral density and bone mass in different age groups were evaluated, and the relevance ratio of osteoporosis in different parts of the subjects was calculated. Elbow venous blood was collected on an empty stomach, and the gender differences of serum bone metabolic markers were detected and compared.

Results: The level of β-CTX was(0.27±0.12) ng /ml, procollanen type 1 N-terminal propeptide(P1NP) was(51.03± 22.36) ng /ml, 25(OH) D3 was (16.68±6.24) ng /ml, serum calcium was(2.34±0.09) mmol / L, blood phosphorus was (1.43± 0.37) mmol / L, and blood magnesium was (0.94±0.07) mmol / L, alkaline phosphatase was (79.28±20.48) U/ L, parathyroid hormone was (3.09±1.60) pmol / L, osteocalcin was (13.29±6.65) ng /ml. Except for blood magnesium, the other indexes had significant differences between different sex groups(P<0.05). Results of T value of bone mineral density and level of bone mass showed that bone mineral density of lumbar vertebrae and both hips fluctuated and decreased with the increase of age, and there were significant differences in level of bone mass among different age groups in women(P<0.05), and except lumbar vertebrae in males, there were significant differences in other parts of bone mass among different age groups (P<0.05). The relevance ratio of lumbar osteoporosis, left hip osteoporosis, and right hip osteoporosis was 27.89%, 14.80% and 14.47%, respectively.

Conclusion: There are obvious differences in relevance ratio of osteoporosis and low bone mass among different sites. It is suggested that the clinical diagnosis of osteoporosis should be combined with bone mineral density and bone metabolic markers. With the increasing prevalence of osteoporosis among middle aged and elderly people in Beijing community, continuous follow-up research based on community primary health care units could promote early examination, early diagnosis, and early treatment of middle aged and elderly people at high risk of osteoporosis in community.

Keywords: Aged; Bone mineral density; Cross sectional study; Middle aged; Osteoporosis.

Background: Long-term treatment with corticosteroids causes loss of bone density, but the effects of using short-term high-dose systemic-corticosteroid therapy to treat acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are unclear. Our aim was to determine whether high-dose corticosteroid therapy affected bone turnover markers (BTMs) to a greater extent compared to low-dose corticosteroid therapy.

Methods: The CORTICO-COP trial (NCT02857842) showed that an eosinophil-guided corticosteroid intervention led to approximately 60% lower accumulated corticosteroid dose for hospitalized patients with AECOPD (low-dose group) compared with 5-day standard corticosteroid treatment (high-dose group). We compared the levels of BTMs C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP) in 318 participants during AECOPD and at 1- and 3-month follow-up visits.

Results: CTX decreased and P1NP increased significantly over time in both treatment groups. There were no significant differences between the groups at 1- or 3-months follow-up for P1NP. A significant drop in CTX was seen at 3 months (down Δ24% from the baseline, p = 0.017) for the high dose group.

Conclusion: Short-term, high-dose systemic corticosteroid treatment caused a rapid suppression of biomarkers of bone resorption. Corticosteroids did not suppress biomarkers of bone formation, regardless of patients receiving low or high doses of corticosteroids. This therapy was, therefore, harmless in terms of bone safety, in our prospective series of COPD patients.

Trial registration: ClinicalTrials.gov Identifier: NCT02857842 . Submitted August 2nd, 2016.

Keywords: Adverse effects; Bone remodelling; Bone turnover markers; Chronic obstructive pulmonary disease; Corticosteroids.

Background: Little is known about the clinical value of Insulin-like growth factor-binding protein-7 (IGFBP7), a cellular senescence marker, in an elderly general population with multiple co-morbidities and high prevalence of asymptomatic cardiovascular ventricular dysfunction. Inflammation and fibrosis are hallmarks of cardiac aging and remodelling. Therefore, we assessed the clinical performance of IGFBP7 and two other biomarkers reflecting these pathogenic pathways, the growth differentiation factor-15 (GFD-15) and amino-terminal propeptide of type I procollagen (P1NP), for their association with cardiac phenotypes and outcomes in the PREDICTOR study.

Methods: 2001 community-dwelling subjects aged 65-84 years who had undergone centrally-read echocardiography, were selected through administrative registries. Atrial fibrillation (AF) and 4 echocardiographic patterns were assessed: E/e' (> 8), enlarged left atrial area, left ventricular hypertrophy (LVH) and reduced midwall circumference shortening (MFS). All-cause and cardiovascular mortality and hospitalization were recorded over a median follow-up of 10.6 years.

Results: IGFBP7 and GDF-15, but not P1NP, were independently associated with prevalent AF and echocardiographic variables after adjusting for age and sex. After adjustment for clinical risk factors and cardiac patterns or NT-proBNP and hsTnT, both IGFBP7 and GDF-15 independently predicted all-cause mortality, hazard ratios 2.13[1.08-4.22] and 2.03[1.62-2.56] per unit increase of Ln-transformed markers, respectively.

Conclusions: In a community-based elderly cohort, IGFBP7 and GDF-15 appear associated to cardiac alterations as well as to 10-year risk of all-cause mortality.

Keywords: Cardiac remodelling; Community-dwelling elderly; GDF-15; IGFBP7; P1NP.

There is limited understanding of how asfotase alfa affects mineral metabolism and bone turnover in adults with pediatric-onset hypophosphatasia. This study showed that adults with hypophosphatasia treated with asfotase alfa experienced significant changes in biochemical markers of bone and mineral metabolism, possibly reflecting enhanced bone remodeling of previously osteomalacic bone.

Introduction: Hypophosphatasia (HPP), due to a tissue nonspecific alkaline phosphatase (TNSALP) deficiency, can cause impaired bone mineralization and turnover. Although HPP may be treated with asfotase alfa, an enzyme replacement therapy, limited data are available on how treatment with asfotase alfa affects mineral metabolism and bone turnover in adults with HPP.

Methods: ALP substrates, bone turnover and mineral metabolism markers, and bone mineral density (BMD) data from EmPATHY, a single-center, observational study of adults (≥ 18 years) with pediatric-onset HPP treated with asfotase alfa (NCT03418389), were collected during routine clinical care and analyzed from baseline through 24 months of treatment.

Results: Data from 21 patients showed significantly increased ALP activity and reduced urine phosphoethanolamine (PEA)/creatinine (Cr) ratios after baseline through 24 months of asfotase alfa treatment. There were significant transient increases in parathyroid hormone 1-84 (PTH), osteocalcin, and procollagen type 1 N-propeptide (P1NP) levels at 3 and 6 months and in tartrate-resistant acid phosphatase 5b (TRAP5b) levels at 3 months, with a significant decrease in N-terminal telopeptide of type 1 collagen (NTX) levels at 24 months. Lumbar spine BMD T scores continuously increased during treatment.

Conclusion: Significant changes in bone turnover and mineral metabolism markers after asfotase alfa treatment suggest that treatment-mediated mineralization may enable remodeling and bone turnover on previously unmineralized surfaces. Urine PEA/Cr ratios may be a useful parameter in monitoring treatment during routine care.

Keywords: Alkaline phosphatase; Bone mineral density; Bone turnover; Enzyme replacement therapy; Hypophosphatasia.

Background: Low muscle mass and osteoporosis are commonly observed in individuals with type 2 diabetes mellitus (T2DM). We investigated the prevalence of low muscle mass and osteoporosis in patients with T2DM who had high glycated hemoglobin (HbA1c) levels.

Methods: We included 187 Chinese patients with T2DM who were aged ⩾50 years and evaluated their body composition using dual-energy X-ray absorptiometry. We measured levels of fasting blood glucose, HbA1c, B collagen-specific sequences (B-CTX), osteocalcin (OC), propeptide of type 1 procollagen (P1NP), and 25-hydroxy vitamin D.

Results: Of the total patients, 82 were men and 105 were women. The prevalence rates of low muscle mass, osteopenia, and osteoporosis were 35.8%, 38.0%, and 31.0%, respectively. The prevalence rate of low muscle mass was significantly higher in women with HbA1c levels >9.0% than in those with HbA1c levels <9.0%. The prevalence rates of osteopenia and osteoporosis in men with HbA1c levels >9.0% differed significantly from those with HbA1c levels <9.0%. The appendicular skeletal muscle mass index (ASMI), trunk muscle mass, lumbar spinal bone mineral content (BMC), lumbar spine BMD, femoral BMC, and femoral BMD were significantly decreased, and the serum levels of B-CTX, OC, and P1NP were significantly increased in patients with T2DM who had osteoporosis. The ASMI was associated with osteopenia/osteoporosis in men and women with T2DM.

Conclusions: In patients with T2DM, high HbA1c levels were associated with higher prevalence rates of low muscle mass in women and osteoporosis in men, and ASMI was a risk factor of osteoporosis.

Keywords: glycated hemoglobin; low muscle mass; osteoporosis; type 2 diabetes mellitus.

Pregnancy- and lactation-associated osteoporosis (PLO) is a rare disease, presenting in most cases with severe back pain due to low energy vertebral fractures (VFs). Our purpose was to assess the effect of teriparatide (TPTD) vs. conventional management on areal bone mineral density (aBMD) and trabecular bone score (TBS) in patients with PLO. A multicenter retrospective cohort study concerning premenopausal women with PLO. Nineteen women were treated with TPTD (20 μg/day) (group A) plus calcium and vitamin D and eight women with calcium and vitamin D only (group B) for up to 24 months. The primary end-point was between group differences in lumbar spine (LS) and total hip (TH) aBMD, and TBS at 12 and 24 months. Patients in group A had sustained a median of 4.0 VFs (3-9) vs. 2.5 VFs (1-10) in group B (p = 0.02). At 12 months, patients on TPTD vs. controls achieved a mean aBMD increase of 20.9 ± 11.9% vs. 6.2 ± 4.8% at the LS (p < 0.001), 10.0 ± 11.6% vs. 5.8 ± 2.8% at the TH (p = 0.43), and 6.7 ± 6.9% vs. 0.9 ± 3.7% in TBS (p = 0.09), respectively. At 24 months, seven patients on TPTD and six controls achieved a mean LS aBMD increase of 32.9 ± 13.4% vs. 12.2 ± 4.2% (p = 0.001). P1NP levels during the first month of TPTD treatment were positively correlated with the 1-year LS aBMD change (r = 0.68, p = 0.03). No new clinical fractures occurred while on-treatment. In patients with PLO, TPTD treatment resulted in significantly greater increases in LS aBMD compared with calcium and vitamin D supplementation at 12 and 24 months.

Keywords: Pregnancy and lactation-associated osteoporosis; Premenopausal women; Teriparatide; Vertebral fractures.

The present work was aimed to evaluate the effect of different administration modes of sodium valproate (VPA) on bone strength, bone mass and bone mineral density in ovariectomized (OVX) rats and further investigation of the possible mechanism. 60 female SD rats were randomly divided into 4 groups: Sham group (Sham, n = 15), OVX group (OVX, n = 15), OVX rats received intermittent VPA treatment group (IVPA, n = 15) and OVX rats received daily VPA treatment group (EVPA, n = 15). After 12 weeks of treatment, the rats were sacrificed, and serum and femur samples were harvested. DEXA, Micro-CT, history, biomechanical testing, biochemical index and western blot analysis were used to observe the therapeutic effect and explore the possible mechanism. Micro-CT and DEXA analysis of bones revealed better BMD and higher BV/TV, Tb. Th, Tb. N, Conn. D and lower Tb. Sp at femoral metaphysis evaluated in IVPA when compared with OVX and EVPA group (P < 0.05). Histological, fluorescent analysis and biological strength revealed more trabecular bone and higher relative mineral apposition rate, maximal load, elastic modulus and energy at break with evaluated in IVPA when compared with OVX and EVPA group (P < 0.05). The levels of P1NP, estrogen, CTX, TRAP-5b and RANKL of the IVPA group showed a significant increase when compared with the OVX and EVPA group (P < 0.05). We confirm adverse effects on protein expressions including Notch1, Jagged1, HEY1, Wnt 1, β-catenin and RUNX2 following daily VPA treatment in OVX female rats. Our current study demonstrated that intermittent administration of sodium valproate has a protective effect on bone health in OVX rats and these effects may be achieved by activating Notch/Wnt/β-catenin/RUNX2 signal axis.

Keywords: Bone mass; Bone mineral density; Bone strength; Osteoporosis; Valproic acid.

Background: Oxidative stress in children with type 1 DM (T1DM) may negatively affect the bone.

Methods: This study included 40 children with T1DM as the patient group and 40 healthy children as the control group. Plasma alkaline phosphatase, procollagen type-1 amino-terminal propeptide (P1NP), and urinary deoxypyridinoline (DPD) were measured to assess bone turnover. Glutathione, superoxide dismutase (SOD), and malondialdehyde (MDA) were measured to assess oxidative stress.

Results: Patients with T1DM had a significantly lower P1NP level but a significantly higher urinary DPD level compared to the control group. Moreover, there were significantly lower glutathione and SOD levels with significantly higher MDA levels in patients with T1DM. We found a significant positive correlation between P1NP level and both glutathione and SOD levels but a significant negative correlation between P1NP and MDA in patients with T1DM. There was a significant negative correlation between DPD levels and both glutathione and SOD levels and a significant positive correlation between DPD and MDA. Moreover, glutathione was a significant predictor for both P1NP and DPD levels, while MDA was a significant predictor for P1NP levels.

Conclusions: There is an association between oxidative stress and bone turnover markers in children with T1DM.

Impact: Oxidative stress can negatively affect bone but the exact relationship between oxidative stress and bone turnover in T1DM has not been previously studied in pediatrics.For the best of our knowledge, our study was the first to assess the relationship between oxidative stress and bone turnover in children with T1DM.We revealed that increased oxidative stress in children and adolescents with T1DM may be involved in the impairment of bone turnover process, so treatment strategies toward better glycemic control and decreasing oxidative stress may be beneficial in preventing and treating diabetic bone disease in these children.

Objective: To evaluate the antiresorptive-cytokine effects of chondroitin sulfate on non-specific lower back pain in patients with knee osteoarthritis (OA).

Materials and methods: Using the envelope method, 231 patients were randomized into two groups: group 1 (n=116, main) received nonsteroidal anti-inflammatory drugs (NSAIDs) and chondrogard, group 2 (n=115, comparison) received only NSAIDs. The 2-month study included 3 visits (V): V₁ - at the beginning of the study, V₂ - after 10 days, V₃ - after 60 days with the assessment of blood parameters: transforming growth factor β1 (TFR β1), interleukin (IL)-1β and IL-6, beta-Crosslaps, bone matrix formation indicator P1NP (n-terminal propeptide procollagen type 1), and determination of the level of deoxypyridinoline (DPID) in the urine.

Results and conclusion: At the end of the study, there is a significant decrease in all studied cytokines in patients of group 1 compared to group 2, as well as indicators of beta-Crosslaps (p<0,001) and DPID (p<0,001), which may indicate the presence of its own antiresorptive-cytokine effect in chondroitin sulfate.

Цель исследования: Оценка антирезорбтивно-цитокиновой эффективности хондропротективной терапии хондроитина сульфатом неспецифической боли в нижней части спины у пациентов с остеоартритом (ОА) коленных суставов.

Материал и методы: Методом конвертов проведена рандомизация в две группы 231 пациента с болью в нижней части спины: больные 1-й группы (n=116, основная группа) получали нестероидные противовоспалительные препараты (НПВП) и препарат Хондрогард, пациенты 2-й группы (n=115, группа сравнения) — только НПВП. В течение 2 мес наблюдения состоялось 3 визита (V): V₁ в начале исследования, V₂ через 10 дней, V₃ через 60 дней с оценкой показателей крови, таких как трансформирующий фактор роста β1 (TGF β1), интерлейкин (IL)-1β, IL-6, Beta-Crosslaps, показатель формирования костного матрикса P1NP (N-терминальный пропептид проколлагена 1-го типа) и определением в моче уровня дезоксипиридинолина (ДПИД).

Заключение: На момент окончания исследования получены результаты статистически значимого снижения всех изучаемых цитокинов у пациентов 1-й группы в сравнении с пациентами 2-й группы, а также показателей Beta-Crosslaps (p<0,001) и ДПИД (p<0,001), что может свидетельствовать о наличии собственного антирезорбтивно-цитокинового эффекта у хондроитина сульфата.

Keywords: Chondroguard; bone resorption; chondroitin sulfate; chondroprotectors; inflammaging; inflammation cytokines; knee osteoarthritis; lower back pain.

Background: It has been reported that serum periostin levels are significantly higher in postmenopausal patients with osteoporotic fractures. Nonetheless, the levels of serum periostin in postmenopausal women with different bone mass remain unclear.

Purpose: The objective of the study was to identify the levels of serum periostin in Chinese postmenopausal women with different bone mass, and the correlations between the periostin levels and the classical bone turnover markers (BTMs), and bone mineral densities (BMDs) at different sites.

Patients and methods: This study enrolled 331 Chinese postmenopausal women in Shanghai; their clinical features were collected; their levels of serum periostin and traditional BTMs were measured by ELISA or the fully automated immunoassay analyzer; their BMDs at different sites were measured by dual-energy X-ray absorptiometry (DXA).

Results: According to the T-value of bone mineral density (BMD), these postmenopausal women were divided into normal group (n=84), osteopenia group (n=126) and osteoporosis group (n=121). There was no significant difference in the serum periostin levels among the above three groups of subjects. In addition, Spearman correlation analysis also revealed that no correlation was observed between the value of serum periostin and those of traditional BTMs, and BMDs at different sites, respectively. The values of traditional BTMs were negatively correlated with those of BMDs at all measured sites. Furthermore, the receiver-operating characteristic (ROC) curves analysis indicated that among the periostin and traditional BTMs mentioned above, the best predictors for postmenopausal osteoporosis in Shanghai Chinese postmenopausal women were osteocalcin (OC) and procollagen type 1 N-terminal propeptide (P1NP) [the areas under the ROC curve (AUC)=0.746 and 0.761, respectively].

Conclusion: Serum periostin may not be used as a marker of systemic bone metabolism in Shanghai Chinese postmenopausal women without prior fracture. In addition, serum P1NP and OC levels may be the predictors of osteoporosis occurrence in Chinese postmenopausal women.

Keywords: bone mineral density; bone turnover markers; periostin; postmenopausal women.

The aim of the work was to find out whether markers of bone formation can be early predictors of osteoporosis in patients with COPD. The study involved 66 patients with COPD with disease duration from 10 to 30 years, age 53.59±12.83 years. 37 (66.06%) patients smoked, the pack / year index was (29.08±16.62). According to the results of CAT testing, all patients were divided into 4 clinical groups: GOLD I-IV. The content of serum markers of bone formation was determined: N-terminal procollagen type I propeptide (PINP), osteocalcin and vitamin D depending on the age and severity of COPD. A decrease in all markers of bone formation was found with the age of patients and the severity of COPD. Thus, in patients under 45 years, the P1NP level was 48.75% higher than in patients aged 75 and older (p<0.001). A significant relationship was established between the age of patients and the P1NP level (r= -0.46; p=<0.05). With GOLD I, a decrease in the P1NP content was observed in 40.0% of patients, with GOLD II - 48.0%, GOLD III - in 45.0%, and with GOLD IV, such a decrease was in 66.67% of patients. The level of osteocalcin decreased in patients with COPD of old age compared with the control by 2.72 times and in young people - by 1.88 times. With GOLD I, a decrease in osteocalcin content was observed in 66.67%, with GOLD II - 89.0%, GOLD III - in 85.0%, and with GOLD IV, a decrease was observed in all (100%) patients. The concentration of vitamin D was reduced in all patients with COPD, and severe vitamin D deficiency was diagnosed in 23.08% of patients under 45 years, in 70.59% of elderly patients, in 100% of elderly people. Among the representatives of GOLD IV, the level of vitamin D decreased by 1.75 times as compared with patients with GOLD I. A severe form of vitamin D deficiency was diagnosed in 46.67% of patients with GOLD I, 40.0% in GOLD II, 65.0% in GOLD III, and in 100% of patients with GOLD IV. The data obtained indicate that with increasing age and increasing severity of COPD, the formation of markers of bone tissue formation is inhibited. These processes occur against the background of vitamin D deficiency. As a result of this imbalance, favorable conditions are created for the development of osteoporosis. Considering that the first signs of these disorders, in particular a decrease in the levels of vitamin D and osteocalcin, are diagnosed already with GOLD I, it can be argued that COPD is the leading factor.

Bone loss is one of the most common complications of immobilization after spinal cord injury (SCI). Whether TGF-β signaling plays a role in SCI-induced disuse bone loss has not been determined. Thus, 16-week-old male mice underwent sham or spinal cord contusion injury to cause complete hindlimb paralysis. Five days later, 10 mg/kg/day control (IgG) or anti-TGF-β1,2,3 neutralizing antibody (1D11) was administered twice weekly for 4 weeks. Femurs were examined by micro-computed tomography scanning (micro-CT) and histology. Bone marrow (BM) supernatants were analyzed by ELISA for levels of procollagen type 1 intact N-terminal propeptide (P1NP), tartrate-resistant acid phosphatase (TRAcP-5b), receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin (OPG), and prostaglandin E2 (PGE2). Distal femoral micro-CT analysis showed that SCI-1D11 mice had significantly (P<0.05) attenuated loss of trabecular fractional bone volume (123% SCI-1D11 vs 69% SCI-IgG), thickness (98% vs 81%), and connectivity (112% vs 69%) and improved the structure model index (2.1 vs 2.7). Histomorphometry analysis revealed that osteoclast numbers were lower in the SCI-IgG mice than sham-IgG sham control. Biochemically, SCI-IgG mice had higher levels of P1NP and PGE2 but similar TRAcP-5b and RANKL/OPG ratio to the sham-IgG group. SCI-1D11 group exhibited higher levels of P1NP and RANKL/OPG ratio but similar TRAcP-5b and PGE2 to the sham-1D11 group. Furthermore, 1D11 treatment prevented SCI-induced hyperphosphorylation of tau protein in osteocytes, an event that destabilizes the cytoskeleton. Together, inhibition of TGF-β signaling after SCI protects trabecular bone integrity, likely by balancing bone remodeling, inhibiting PGE2 elevation, and preserving the osteocyte cytoskeleton.

Keywords: TGF-β; bone; immobilization; spinal cord injury; tau; unloading.

BACKGROUND

In the past few years, a distinct and multifactorial clinical entity called chronic kidney disease-mineral and bone disorder (CKD-MBD) that leads to decreased bone density and osteoporosis has been identified. The aim of this study was to assess the levels of the matrix metalloproteinase-1 and -2 (MMP-1 and MMP-2) in chronic kidney disease (CKD) patients of various disease stages in correlation to other bone turnover markers (BTM). This study is an initial investigative approach to a possible role of matrix metalloproteinases (MMPs) in the evaluation of bone disease in uremic patients.

METHODS

We enrolled 60 patients at different stages of pre-dialysis CKD, 20 patients on hemodialysis (HD), and 20 age-matched healthy controls. Serum intact parathyroid hormone (iPTH), osteocalcin (OC), N-terminal propeptide of type I collagen (P1NP), and beta-C-terminal telopeptide of type I collagen (β-CTX), were measured by electrochemiluminescence on automatic analyzers. Serum MMP-1 and MMP-2 levels were estimated using a commercial enzyme-linked immunosorbent assay (ELISA). Serum levels of urea, creatinine, calcium, phosphorus, and alkaline phosphatase were estimated. Creatinine clearance (ClCr) was calculated using the traditional clearance formula based on a 24-hour urine collection.

RESULTS

Serum iPTH, OC, P1NP, β-CTX concentrations were significantly higher (p <0.0001) while ClCr was significantly lower (p <0.0001) in CKD patients, as compared with those of healthy controls. A positive correlation was established between serum MMP-1 and OC levels (r =0.245, p =0.014), as well as with serum β-CTX levels (r =0.197, p =0.048), and a negative correlation between MMP-2 and OC (r =-0.222, p =0.025).

CONCLUSIONS

In CKD patients MMP-1 serum levels may reflect increased bone turnover rates. HIPPOKRATIA 2017, 21(1): 25-31.

The aim of this study was to investigate the features of bone metabolism and their influence on the arterial wall stiffness in postmenopausal women with a controlled uncomplicated arterial hypertension (AH). The study involved 44 women (main group) with the mean age of 69.04±0.72 years and a postmenopausal duration of 18.4±0.85 years, suffering from an AH grade 2, and 30 healthy patients (control group), their mean age being 69.3±1.21 years, postmenopausal duration 19.4±1.18 years (p>0.05). All patients underwent general clinical and laboratory examination with determination of lipid level in blood. Pulse wave analysis (SphygmoCor) parameters , Bone mineral density (BMD) were assessed. The levels of 25(OH) D, parathyroid hormone, propeptide procollagen of type 1 aminoterminal (P1NP), b-isomerized C-terminal telopeptides (b-CTx), ionized calcium and phosphorus in serum were assessed. The data obtained from the study of the parameters of applanation tonometry and the structural and functional state of bone tissue in patients with an uncomplicated hypertension at the age of 69±3.30 years manifest the likelihood of joint pathogenetic mechanisms of developing atherocalcinosis, increased vascular stiffness and impending osteoporosis.